Peptides play a key role as structural and functional elements in biochemistry/pharmacology and immunology. The fascination with the development of solid phase peptide synthesis (SPPS) stimulated considerable research towards the development of new methodologies, strategies and tactics in peptide synthesis. The efficiency of polymeric support is still a prior suspect in solid phase peptide synthesis. The success of peptide bond formation depends to some extent on the macromolecular characteristics of the crosslinked polymer support used. During the last two decades, several attempts were made to develop hydrophilic supports instead of the rigid, hydrophobic Merrifield resin. The systematic and quantitative research leads to the development of some hydrophilic flexible polymer supports, which show optimum characteristics in solid phase reactions, especially in solid phase peptide synthesis.
Synthesis of biologically active proteins and peptide sequences is significant in revealing the structure-activity correlation and to establish their conformation pattern. The solid phase peptide synthesis reported by Merrifield has made an inestimable contribution to the synthesis of biologically and medicinally important polypeptides.
As the peptide chain grows on the polymer support, its physiochemical properties influence the solvation characteristics of the peptide-bearing support. Therefore, a more ideal support would be one in which the physiochemical characteristics of the support resembles those of the growing peptide chain.
Thus Sheppard and coworkers introduced the polar polyacrylamide based supports. But these supports swell only in polar solvents like dimethylformamide (DMF), dimethylacetamide (DMA) etc. A more compromising situation would be the supports, which are amphiphilic in nature, i.e., which swell in both the polar, and the non-polar solvents employed in peptide synthesis.
Since Merrifield's original report over three decades ago describing solid phase synthesis of a simple tetra peptide on low crosslinked polystyrene beads, the approach has been improved and generalized to the synthesis of complicated peptides, long oligonucleotides and a myriad of small organic molecules. The success of such efforts is often affected by the choice of polymeric support, with regard to mechanical stability, swellablity, compatibility with a range of hydrophilic and/or hydrophobic solvents, and applicability to both batch wise and continuous flow reactors. The selection of possible supports introduced and tested over the years includes polyamides, polyamide composites, polyethylene-polystyrene films, cotton and other carbohydrates, controlled pore silica glass, polyethylene glycol-polystyrene (PEG-PS and Tentagel) graft resins.
Comparing all of these available polymeric supports the newly synthesized propoxylate function of hexanediol diacrylate gives considerable yield and purity. The outcome of a multistep solid-phase synthesis is dependent on the structure of the peptide to be prepared, the strategy followed, as well as the type of solid support employed. In order to ensure a proper solvation of the reactive species allowing fast and quantitative reactions, their polarity must also be compatible with those of the reagents and solvents used, as well as with these of the resin-bound growing peptide. Other styrene-based resins arising so many problems in SPPS, their mechanical stability and flexibility of the crosslinks are low compared with the newly developed system of propoxylate crosslinks. The polyethylene glycol based systems are showing high flexibility, but showing least mechanical stability cause steric problems in the entire system. Solid phase synthesis of peptides has witnessed dramatic progress since its inception. Various polymer supports, new linkers, protection schemes and coupling methods have since made the technique simple and almost foolproof. Sequence specific problems are some of the main problems in peptide synthesis. In solid phase peptide synthesis the sequence specific problem is present irrespective of resin type. Sequence specific problems have been found to be the result of the formation of β-sheet formation can bring additional cross-linking within the matrix; the synthesis of sequences favoring such secondary structures by SPPS will be difficult even if we use the supports having high swelling characteristics. Studies have shown that the formation of β-sheet structure is accompanied by a drastic decrease in swelling and solvation of the peptidyl resin. Thus, the main criteria in choosing a support for peptide synthesis is that it should be compatible with the peptide towards all the solvents used for the synthesis and capable of suppressing the β-sheet forming tendency of the growing peptide.
Thus there are several drawbacks and disadvantages in the prior art discussion of available resins, with this view in mind pointing out a styrene based polymer support having regulated flexibility, to avoid aggregation and β-sheet formation but still having swellablity in a wide range of solvents, a new polymeric support propoxylate function of hexanediol diacrylate crosslinked with polystyrene in bead form was synthesized. This polymer were found to be more easily swollen in both polar and non-polar solvents.